Dianthus Therapeutics, Inc. · NASDAQ:DNTH

Dianthus Therapeutics — Virtual Industry Forum (2025)

27 slides from Dianthus Therapeutics's conference presentation, 2025

  1. Slide 1: Upstream Targeting: Rethinking MG Treatment Through Active C1s Inhibition

    Upstream Targeting: Rethinking MG Treatment Through Active C1s Inhibition e * Expert Panel 4 ~ PUSHPA STOJAN SHAHAR NARAYANASWAMI PERIC SHELLY MD MD, PHD MD

  2. Slide 2: Agenda

    AGENDA Introduction to dianthus therapeutics and claseprubart Clinical and treatment gaps Panel discussion part 1: clinical and treatment gaps aC1s inhibition mode of action animation Upstream inhibition of the classical pathway MaGic phase 2 results Panel discussion part 2: feedback on MaGic result

  3. Slide 3: Selectively targeting classical pathway aims to provide effective but safer complement inhibition

    Selectively targeting classical pathway aims to provide effective but safer complement inhibition Targeting aC1s aims to deliver efficacy demonstrated with terminal inhibitors while preserving the critical immune activity of lectin and alternative pathways, leading to a lower risk of infection and n

  4. Slide 4: C1s is a clinically validated target in the classical complement pathway with an FDA approved therapy

    Cis is a clinically validated target in the classical complement pathway with an FDA approved therapy 0) Classical pathway The only pathway activated by the presence of IgG and IgM, which bind to the C1 complex The C1 complex The initial component of the classical complement pathway consisting of C1

  5. Slide 5: Claseprubart phase 1 data confirms potent inhibition of the classical pathway as a Q2W S.C. injection

    Claseprubart phase 1 data confirms potent inhibition of the classical pathway as a Q2W S.C. injection Ph. 1 Data Confirms ~60-day half-life IC90 calculated at 87 ug/mL Dosing Modeled 15mg/kg I.V. on Day 0 300mg S.C. Q2W starting Day 7 300 100 DNTH103 Concentration (ug/mL) a Oo ° Day 0: 15mg/kg LV. S

  6. Slide 6: Claseprubart in vitro study indicates lower risk of neisseria meningitidis infections

    Claseprubart in vitro study indicates lower risk of neisseria meningitidis infections * Protection against infection is a critical function of the complement pathway ¢ DNTH103 selectively inhibits the classical pathway, leaving the alternative and lectin-activated defense pathways intact + Anin vitr

  7. Slide 7: Claseprubart rapidly advancing in three clinical trials with multiple catalysts in 2026

    Claseprubart rapidly advancing in three Clinical trials with multiple catalysts in 2026 Program (Target) Target Population 2024 2025 2026 Generalized Myasthenia Ph. 2 MaG Gravis (gMG) reported Q; >100,000 U.S. patients Claseprubart Multifocal Motor (S.C. Active C1s Neuropathy (MMN) Initiated Ph. 2 t

  8. Slide 8: Pro-inflammatory split products C3a and C3b have potential negative effects on NMJ pathology beyond MAC in gMG

    Pro-inflammatory split products C3a and C3b have potential negative effects on NMJ pathology beyond MAC in gMG Classical pathway Antibody-antigen complex C1q, Ctr Active C1s inhibitor claseprubart acts upstream from C3 Shared terminal pathway (C5) Y Autoantibodies activate the classical pathway of c

  9. Slide 9: Pro-inflammatory split products C3a and C3b have potential negative effects on NMJ pathology beyond MAC in gMG

    Pro-inflammatory split products C3a and C3b have potential negative effects on NMJ pathology beyond MAC in gMG C3a and C3b Are Elevated in AChR+ gMG — Both Cause Inflammatory Damage’ C3a C3b ¢ Anaphylotoxin?? IL-6 in gMG? NMJ via smooth * Initiates mast cell degranulation? « Forms part of an amplifi

  10. Slide 10: Claseprubart potently prevents the creation of pro-inflammatory split products C3a and C3b vs ravulizumab

    Claseprubart potently prevents the creation of pro-inflammatory split products C3a And C3b vs ravulizumab C3a Formation’ C3b Deposition?” 10 5 § 100 5 ara 0 Pee ee ee) ee Ft 2 koe ee Cee = 4 bo S204 3 = 2 c ™ 604 & 404 ce) 3 s 3 = 40 4 ao fed 604 Claseprubart oO -e Claseprubart Dy -= Ravulizumab @ 2

  11. Slide 11: Presentation at the AANEM Annual Meeting: top-line results for MaGic

    Presentation at the AANEM Annual Meeting, October 29 — November 1, 2025, San Francisco, California Top-line results for MaGic, a phase 2 trial of claseprubart (DNTH103), an active Cis inhibitor, in generalized myasthenia gravis Pushpa Narayanaswami,* Sankalp Gokhale, Caitlin M Briggs, Uzma Siddiqui,

  12. Slide 12: Disclosures

    Disclosures Pushpa Narayanaswami has received research support from AHRQ, PCORI, NIH, Alexion. She has served as advisor/consultant for Alexion/ Astra-Zeneca, Argenx, Amgen, Cartesian, CVS, Dianthus Therapeutics, EMD-Serono, GSK, Immuneabs, Immunovant, Johnson & Johnson, Novartis, UCB, Viridian. She

  13. Slide 13: Introduction

    Introduction Active C1s inhibitor * Claseprubart (DNTH103) targets the classical erick claseprubart acts complement pathway through active C1s (aC‘1s) e7/) Antibody upstream from C3 inhibition. antigen complex * Claseprubart is the first aC1s inhibitor evaluated F in generalized myasthenia gravis (g

  14. Slide 14: MaGic is a global Ph. 2 trial in AChR antibody + gMG patients

    MaGic is a global Ph. 2 trial in AChR antibody + gMG patients A global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and PK/PD of claseprubart administered SC following initial loading dose Highlights + Design: ~60 male and female subjects randomi

  15. Slide 15: Participant baseline characteristics were generally well balanced across arms

    Participant baseline characteristics were generally well balanced across arms Claseprubart Claseprubart AChR antibody + gMG participants 300mg Q2W 600mg Q2W 2) (N=22) ‘Age, mean (SD), years 52.2 (16.5) 57.1 (13.7) 55.3 (12.0) Male, n (%) 13 (59%) 14 (67%) 10 (45%) Weight, mean (SD), pounds 195.0 (48

  16. Slide 16: Claseprubart was generally well tolerated, with a favorable, potentially differentiated safety profile in Phase 2

    Claseprubart was generally well tolerated, with a favorable, potentially differentiated safety profile in Phase 2 Placebo | Claseprubart 300mg Q2W | Claseprubart 600mg Q2W (N=22) (n=21) (n=22) Clinical adverse events (AEs)\) 11 (50.0%) 13 (61.9%) 15 (68.2%) Related serious AEs 1 (4.5%) 0 (0%) 0 (0%)

  17. Slide 17: Claseprubart arms demonstrated rapid, sustained, and clinically meaningful improvements in MG-ADL score

    Claseprubart arms demonstrated rapid, sustained, and clinically meaningful improvements in MG-ADL score 0.0 -@- Placebo (n=22) —®- Claseprubart 300mg Q2W (n=21) ~@- Claseprubart 600mg Q2W (n=22) -1.0 g 0 3 BOR ~;~ os eR Ee ee eee a 8 -3.0 : 4 (18) 29 40 Bg Po00113" ____|_P20.0006" e £ 5.0 oO re eS i

  18. Slide 18: Claseprubart arms demonstrated rapid, sustained, and clinically meaningful improvements in QMG score

    Claseprubart arms demonstrated rapid, sustained, and clinically meaningful improvements in QMG score 0.0 —@ Placebo (n=22) —® Claseprubart 300mg Q2W (n=21) —@ Claseprubart 600mg Q2W (n=22) -1.0 -2.0 207 \i™ $$ 2 J OS be fnew nnn een}. eees -3.0 P=0.0144* P=0.0111* -4.0 in QMG Score Mean Change from

  19. Slide 19: >60% of participants on claseprubart achieved ≥2 point improvement in MG-ADL

    >60% of participants on claseprubart 300mg and 600mg achieved 25 point improvement in MG-ADL Improvement in MG-ADL Total Score 211 211 5% 2 210 210 5% ll By 29 11% El 29 10% Hi a8 28 11% 28 14% 5a 27 28% 1 27 29% eq 26 50% I mm 14% 26 52% 1.4% eg 25 61% Wm 24% 25 62% NS 24% as 24 67% a 38% 24 76% I

  20. Slide 20: >60% of participants on claseprubart 300mg achieved ≥3 point improvement in QMG

    >60% of participants on claseprubart 300mg achieved 25 point improvement in QMG Improvement in QMG Total Score 213 6% 213 @ 212 6% Bf 212 Gell 6% Bf ail Be 20 17% MM 5% 210 5% £8 29 22% ME 5% 29 10% ME 5% £m 28 22% MM 14% 28 14% MM 14% 3 F 27 33% I mm 14% 27 29% BM 14% 8 < 26 44% 1m 14% 26 52% 14% e

  21. Slide 21: 37% of 300mg claseprubart-treated participants achieved Minimal Symptom Expression on MG-ADL at Week 13

    37% of 300mg claseprubart-treated participants achieved Minimal Symptom Expression on MG-ADL at Week 13 Minimal Symptom Expression (MSE) % of Participants Achieving MG-ADL Score of 0 or 1 at Week 13 P=0.1031 Placebo Claseprubart 300mg Claseprubart 600mg (Week 13) (Week 13) (Week 13)

  22. Slide 22: Across key efficacy measures, claseprubart demonstrated equally robust and clinically meaningful responses

    Across key efficacy measures, claseprubart demonstrated equally robust and clinically meaningful responses Claseprubart 300mg Q2W Placebo- | adjusted -2.8 4.6 “1.8 (P=0.0113)* -2.4 “2.0 44 (P=0.0144)* 23% 970 14% 37% Es assays 27% -5.6 8 =H. 87 (P=0.0008)* a -2.2 EA “1.5 3.9 6.1 (P=0.0414)* Boy (P=0

  23. Slide 23: Conclusions

    Conclusions ¢ Claseprubart treatment was well tolerated and resulted in clinically meaningful and statistically significant improvements across key assessments * The benefit/risk profile of both doses was similar, supporting research focus on the lower dose ¢ Claseprubart has the potential to delive

  24. Slide 24: Thank you to all our patient participants

    THANK YOU TO ALL OUR PATIENT PARTICIPANTS MaGic Principal Investigators Ana Azanjac-Arsic Cynthia Bodkin Urszula Chyrchel-Paszkiewicz Gordana Djordjevic Dori, Amir Erik Ensrud Marc Feinberg Laura Fionda Folkens, Eric Miriam Freimer Nils Gilhus Raghav Govindarajan Mariusz Grudniak Kelly Gwathmey Ali

  25. Slide 25: Phase 3 trial design pending regulatory feedback

    Phase 3 trial design pending regulatory feedback Evaluate 300mg Q4W based on early PK/PD data from Phase 2 OLE S.C. Treatment Period Claseprubart 300mg SC Q2W Seer oe Claseprubart 300mg SC Q4W Screening Period Open-Label Extension * Primary Endpoint: Change from Baseline to end of RCT in Myasthenia

  26. Slide 26: Mean change in MG-ADL score from baseline at week 13 in patients with QMG ≥10

    Mean change in MG-ADL score from baseline at week 13 in patients with QMG 210 MG-ADL Change from Baseline in All MG-ADL Change from Baseline in Patients Patients with QMG 210 Placebo Claseprubart 300mg Q2W Placebo Claseprubart 300mg Q2W. (n=22) (n=21) (n=16) (n=18) 0.0 & ° Mean Change from Baseline

  27. Slide 27: Rationale for adding 300mg Q4W in addition to 300mg Q2W in future Ph. 3 study

    Rationale for adding 300mg Q4W in addition to 300mg Q2W in future ph. 3 study Mean Change in MG-ADL and QMG Score from RCT Baseline to OLE Week 6 14.2 14.0 12.0 + 10.0 + 8.0 6.0 5 4.0 2.0 ——QMG -—MG-ADL OLE Data Support 300mg Q4W Dosing in Future Ph. 3 Study + Placebo patients switching over to OLE

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